AbstractActivities and physical effort have been commonly estimated using a metabolic rate through indirect calorimetry to capture breath information. The physical effort represents the work hardness used to optimize wearable robotic systems. Thus, personalization and rapid optimization of the effort are critical. Although respirometry is the gold standard for estimating metabolic costs, this method requires a heavy, bulky, and rigid system, limiting the system’s field deployability. Here, this paper reports a soft, flexible bioelectronic system that integrates a wearable ankle-foot exoskeleton, used to estimate metabolic costs and physical effort, demonstrating the potential for real-time wearable robot adjustments based on biofeedback. Data from a set of activities, including walking, running, and squatting with the biopatch and exoskeleton, determines the relationship between metabolic costs and heart rate variability root mean square of successive differences (HRV-RMSSD) (R = −0.758). Collectively, the exoskeleton-integrated wearable system shows potential to develop a field-deployable exoskeleton platform that can measure wireless real-time physiological signals.